The association between glucose intolerance and aging is well documented but the mechanisms contributing to this decline are unclear. Utilizing a newly developed technique, the glucose clamp, in combination with 3H glucose tracer studies, we propose to investigate the relative contributions of: (a) impaired beta cell sensitivity to glucose, (b) diminished tissue sensitivity to insulin, and (c) augmented hepatic glucose production to this age-related deterioration in carbohydrate metabolism. Insulin binding to monocytes will also be determined in each subject and correlated with changes in tissue sensitivity to insulin. The contribution of abnormal glucagon metabolism to the glucose intolerance will be ascertained by examining: (a) glucagon suppressibility following insulin and glucose, (b) glucagon secretion following alanine infusion and the oral ingestion of a protein meal, (c) hepatic glucose production following physiologic increments in plasma glucagon levels, and (d) tissue sensitivity to insulin following selective removal of glucagon with somatostatin. Despite marked changes in body composition with age, there are no available data concerning changes in amino acid metabolism with age. We propose to study age-related changes in amino acid metabolism by examining: (a) the plasma amino acid response to insulin (euglycemic clamp), glucose (hyperglycemic clamp), and the ingestion of a protein meal and (b) overall amino acid utilization as reflected by leucine turnover.